BackgroundThere is an ongoing debate whether primary lateral sclerosis (PLS) should be regarded as an independent disease entity separate from amyotrophic lateral sclerosis (ALS) or as a slowly progressive variant of ALS.

ObjectiveThe study was designed to investigate specific white matter alterations in diffusion tensor imaging (DTI) data from PLS patients by a hypothesis-guided tract-of-interest-based approach compared with ‘classical’ ALS patients and healthy controls, in order to identify microstructural changes according to the neuropathologically defined ALS affectation pattern in vivo.MethodsDTI-based white matter mapping was performed both by an unbiased voxelwise statistical comparison and by a hypothesis-guided tractwise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern for 50 PLS and 50 ALS patients vs 50 matched controls.

ResultsThe analysis of white matter integrity by regional FA reductions demonstrated the characteristic alteration patterns along the CST and also in frontal and prefrontal brain areas in PLS patients and ALS patients. In the tract-specific analysis according to the ALS-staging pattern, PLS and ALS affectation patterns showed identical significant alterations of ALS-related tract systems when compared with controls and no differences when compared with each other.

ConclusionsThis DTI study showed the same microstructural affectation patterns in PLS patients as in ALS, in support of the hypothesis that PLS is a phenotypical variant of ALS.